tbuckley/cabot-search huggingface dataset:
How Do I Honor You? On Caring for LGBTQ+ Patients and Families as an LGBTQ+ Clinician
Authors: Alexis Drutchas, Andrew J. Lawton
Journal: Annals of Internal Medicine (2023)

On Being a DoctorOctober 2023How Do I Honor You? On Caring for LGBTQ+ Patients and Families as an LGBTQ+ ClinicianAlexis Drutchas, MD, Andrew J. Lawton, MDAlexis Drutchas, MDMassachusetts General Hospital; Boston, MassachusettsSearch for more papers by this author, Andrew J. Lawton, MDDana–Farber Cancer Institute; Boston, MassachusettsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M23-1774 Audio Reading - “How Do I Honor You? On Caring for LGBTQ+ Patients and Families as an LGBTQ+ Clinician” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “How Do I Honor You? On Caring for LGBTQ+ Patients and Families as an LGBTQ+ Clinician” by Alexis Drutchas, MD, and Andrew J. Lawton, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Henry looked exhausted by advanced cancer. His partner, Miles, sat dutifully at his bedside when Andrew, his palliative care consultant, walked in. From the doorway, Andrew felt a familiar swell of emotion upon meeting an older gay couple in his practice: a high degree of responsibility and deep sense of privilege. In a hospital across town, Donna winced in pain from progressive cancer. Alexis, her palliative care consultant, had just walked in. “My wife will be in soon,” Donna said nervously. Alexis, too, felt something familiar: a sense of connection and desire for Donna to feel safe and cared for. ... Author, Article, and Disclosure InformationAuthors: Alexis Drutchas, MD; Andrew J. Lawton, MDAffiliations: Massachusetts General Hospital; Boston, MassachusettsDana–Farber Cancer Institute; Boston, MassachusettsCorresponding Author: Alexis Drutchas, MD, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114; e-mail, adrutchas@mgh.harvard.edu. PreviousarticleNextarticle Advertisement Audio Reading - “How Do I Honor You? On Caring for LGBTQ+ Patients and Families as an LGBTQ+ Clinician” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “How Do I Honor You? On Caring for LGBTQ+ Patients and Families as an LGBTQ+ Clinician” by Alexis Drutchas, MD, and Andrew J. Lawton, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics October 2023Volume 176, Issue 10 Page: 1428-1429 ePublished: 17 October 2023 Issue Published: October 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Impact of piperaquine resistance in Plasmodium falciparum on malaria treatment effectiveness in The Guianas: a descriptive epidemiological study
Authors: Celia Florimond, Franck de Laval, Angela M Early, Swaélie Sauthier, Yassamine Lazrek, Stéphane Pelleau, Wuelton M Monteiro, Maxime Agranier, Nicolas Taudon, François Morin, Magda Magris, Marcus V G Lacerda, Giselle M R Viana, Sócrates Herrera, Malti R Adhin, Marcelo U Ferreira, Charles J Woodrow, Ghulam R Awab, Horace Cox, Maria-Paz Ade, Emilie Mosnier, Félix Djossou, Daniel E Neafsey, Pascal Ringwald, Lise Musset
Journal: The Lancet Infectious Diseases (2023)

Plasmodium falciparum is an apicomplexan parasite responsible for lethal cases of malaria. According to WHO recommendations, P falciparum cases are treated with artemisinin-based combination therapy including dihydroartemisinin-piperaquine. However, the emergence of resistant parasites against dihydroartemisinin-piperaquine was reported in southeast Asia in 2008 and, a few years later, suspected in South America.
Emicizumab prophylaxis in patients with acquired haemophilia A (GTH-AHA-EMI): an open-label, single-arm, multicentre, phase 2 study
Authors: Andreas Tiede, Christina Hart, Paul Knöbl, Richard Greil, Johannes Oldenburg, Ulrich J Sachs, Wolfgang Miesbach, Christian Pfrepper, Karolin Trautmann-Grill, Katharina Holstein, Jan Pilch, Patrick Möhnle, Christoph Schindler, Carmen Weigt, Dorothea Schipp, Marcus May, Christiane Dobbelstein, Fabius J Pelzer, Sonja Werwitzke, Robert Klamroth
Journal: The Lancet Haematology (2023)
Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Alexander C Ford, Alexandra Wright-Hughes, Sarah L Alderson, Pei-Loo Ow, Matthew J Ridd, Robbie Foy, Gina Bianco, Felicity L Bishop, Matthew Chaddock, Heather Cook, Deborah Cooper, Catherine Fernandez, Elspeth A Guthrie, Suzanne Hartley, Amy Herbert, Daniel Howdon, Delia P Muir, Taposhi Nath, Sonia Newman, Thomas Smith, Christopher A Taylor, Emma J Teasdale, Ruth Thornton, Amanda J Farrin, Hazel A Everitt, Alexander C. Ford, Alex Wright-Hughes, Sarah L. Alderson, Pei-Loo Ow, Matthew J. Ridd, Robbie Foy, Maggie Barratt, Gina Bianco, Felicity L. Bishop, Richard Brindle, Sarah Brown, Matthew Chaddock, Aimee Christodoulou, Heather Cook, Deborah Cooper, Florence Day, Aaron Dowse, Jill Durnell, Jake Emmerson, Alasdair Fellows, Catherine Fernandez, Elspeth A. Guthrie, Suzanne Hartley, Amy Herbert, Damien Hindmarch, Daniel Howdon, Aminah Malik, Tom Morris, Delia P. Muir, Roberta Longo, Sandra Lopes Goncalves Graca, Taposhi Nath, Sonia Newman, Catriona Parker, Thomas Smith, Christopher A. Taylor, Emma J. Teasdale, Ruth Thornton, Sandy Tubeuf, Amy West, Emma-Jane Williamson, Amanda J. Farrin, Hazel A. Everitt
Journal: The Lancet (2023)

Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting.
Population structure and antimicrobial resistance among Klebsiella isolates sampled from human, animal, and environmental sources in Ghana: a cross-sectional genomic One Health study
Authors: Jessica K Calland, Kaisa Haukka, Stephen W Kpordze, Atanyiwoen Brusah, Marta Corbella, Cristina Merla, Ørjan Samuelsen, Edward J Feil, Davide Sassera, Akosua B Karikari, Courage K S Saba, Harry A Thorpe, Jukka Corander
Journal: The Lancet Microbe (2023)

One Health approaches to address the increasing threat of antimicrobial resistance (AMR) are gaining attention. However, data on the distribution and movement of bacteria and their AMR-associated genes between clinical and non-clinical sources are scarce, especially from low-income and middle-income countries. We aimed to analyse Klebsiella isolates from various sources in Ghana and compare the prevalence of AMR with datasets from two other countries.
Nested Case–Control Studies Investigating Serum Perfluorooctanoate and Perfluorooctane Sulfonate Levels and Pancreatic Ductal Adenocarcinoma in Two Cohorts
Authors: Ting Zhang, Sheng Fu, Kai Yu, Demetrius Albanes, Steven C. Moore, Mark P. Purdue, Rachael Z. Stolzenberg-Solomon
Journal: Environmental Health Perspectives (2023)
Fluorescence lifetime of injected indocyanine green as a universal marker of solid tumours in patients
Authors: Rahul Pal, Thinzar M. Lwin, Murali Krishnamoorthy, Hannah R. Collins, Corey D. Chan, Andrey Prilutskiy, MacLean P. Nasrallah, Tom H. Dijkhuis, Shriya Shukla, Amy L. Kendall, Michael S. Marshall, Stefan A. Carp, Yin P. Hung, Angela R. Shih, Maria Martinez-Lage, Lawrence Zukerberg, Peter M. Sadow, William C. Faquin, Brian V. Nahed, Allen L. Feng, Kevin S. Emerick, J. Sven D. Mieog, Alexander L. Vahrmeijer, Karthik Rajasekaran, John Y. K. Lee, Kenneth S. Rankin, Santiago Lozano-Calderon, Mark A. Varvares, Kenneth K. Tanabe, Anand T. N. Kumar
Journal: Nature Biomedical Engineering (2023)
Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial
Authors: John M. Kirkwood, Michele Del Vecchio, Jeffrey Weber, Christoph Hoeller, Jean-Jacques Grob, Peter Mohr, Carmen Loquai, Caroline Dutriaux, Vanna Chiarion-Sileni, Jacek Mackiewicz, Piotr Rutkowski, Petr Arenberger, Gaelle Quereux, Tarek M. Meniawy, Paolo A. Ascierto, Alexander M. Menzies, Piyush Durani, Maurice Lobo, Federico Campigotto, Brian Gastman, Georgina V. Long
Journal: Nature Medicine (2023)

Abstract Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those with resected stage IIIA/B disease. The phase 3, double-blind CheckMate 76K trial assessed 790 patients with resected stage IIB/C melanoma randomized 2:1 (stratified by tumor category) to nivolumab 480 mg or placebo every 4 weeks for 12 months. The primary endpoint was investigator-assessed recurrence-free survival (RFS). Secondary endpoints included distant metastasis-free survival (DMFS) and safety. At 7.8 months of minimum follow-up, nivolumab significantly improved RFS versus placebo (hazard ratio (HR) = 0.42; 95% confidence interval (CI): 0.30–0.59; P &lt; 0.0001), with 12-month RFS of 89.0% versus 79.4% and benefit observed across subgroups; DMFS was also improved (HR = 0.47; 95% CI: 0.30–0.72). Treatment-related grade 3/4 adverse events occurred in 10.3% (nivolumab) and 2.3% (placebo) of patients. One treatment-related death (0.2%) occurred with nivolumab. Nivolumab is an effective and generally well-tolerated adjuvant treatment in patients with resected stage IIB/C melanoma. ClinicalTrials.gov identifier: NCT04099251 .
Predicting survival in patients with ‘non-high-risk’ acute variceal bleeding receiving β-blockers+ligation to prevent re-bleeding
Authors: Lorenz Balcar, Mattias Mandorfer, Virginia Hernández-Gea, Bogdan Procopet, Elias Laurin Meyer, Álvaro Giráldez, Lucio Amitrano, Candid Villanueva, Dominique Thabut, Luis Ibáñez Samaniego, Gilberto Silva-Junior, Javier Martinez, Joan Genescà, Christophe Bureau, Jonel Trebicka, Elba Llop Herrera, Wim Laleman, José María Palazón Azorín, Jose Castellote Alonso, Lise Lotte Gluud, Carlos Noronha Ferreira, Nuria Cañete, Manuel Rodríguez, Arnulf Ferlitsch, Jose Luis Mundi, Henning Grønbæk, Manuel Nicolas Hernandez Guerra, Romano Sassatelli, Alessandra Dell'Era, Marco Senzolo, Juan Gonzalez Abraldes, Manuel Romero-Gómez, Alexander Zipprich, Meritxell Casas, Helena Masnou, Massimo Primignani, Aleksander Krag, Frederik Nevens, Jose Luis Calleja, Christian Jansen, María Vega Catalina, Agustín Albillos, Marika Rudler, Edilmar Alvarado Tapias, Maria Anna Guardascione, Marcel Tantau, Rémy Schwarzer, Thomas Reiberger, Stig Borbjerg Laursen, Marta Lopez-Gomez, Alba Cachero, Alberto Ferrarese, Cristina Ripoll, Vincenzo La Mura, Jaime Bosch, Juan Carlos García-Pagán
Journal: Journal of Hepatology (2023)
Model metamers reveal divergent invariances between biological and artificial neural networks
Authors: Jenelle Feather, Guillaume Leclerc, Aleksander Mądry, Josh H. McDermott
Journal: Nature Neuroscience (2023)

Deep neural network models of sensory systems are often proposed to learn representational transformations with invariances like those in the brain. To reveal these invariances, we generated 'model metamers', stimuli whose activations within a model stage are matched to those of a natural stimulus. Metamers for state-of-the-art supervised and unsupervised neural network models of vision and audition were often completely unrecognizable to humans when generated from late model stages, suggesting differences between model and human invariances. Targeted model changes improved human recognizability of model metamers but did not eliminate the overall human-model discrepancy. The human recognizability of a model's metamers was well predicted by their recognizability by other models, suggesting that models contain idiosyncratic invariances in addition to those required by the task. Metamer recognizability dissociated from both traditional brain-based benchmarks and adversarial vulnerability, revealing a distinct failure mode of existing sensory models and providing a complementary benchmark for model assessment.
Trimodal single-cell profiling reveals a novel pediatric CD8αα+ T cell subset and broad age-related molecular reprogramming across the T cell compartment
Authors: Zachary Thomson, Ziyuan He, Elliott Swanson, Katherine Henderson, Cole Phalen, Samir Rachid Zaim, Mark-Phillip Pebworth, Lauren Y. Okada, Alexander T. Heubeck, Charles R. Roll, Veronica Hernandez, Morgan Weiss, Palak C. Genge, Julian Reading, Josephine R. Giles, Sasikanth Manne, Jeanette Dougherty, C. J. Jasen, Allison R. Greenplate, Lynne A. Becker, Lucas T. Graybuck, Suhas V. Vasaikar, Gregory L. Szeto, Adam K. Savage, Cate Speake, Jane H. Buckner, Xiao-jun Li, Thomas F. Bumol, E.John Wherry, Troy R. Torgerson, Laura A. Vella, Sarah E. Henrickson, Peter J. Skene, Claire E. Gustafson
Journal: Nature Immunology (2023)

Abstract Age-associated changes in the T cell compartment are well described. However, limitations of current single-modal or bimodal single-cell assays, including flow cytometry, RNA-seq (RNA sequencing) and CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), have restricted our ability to deconvolve more complex cellular and molecular changes. Here, we profile &gt;300,000 single T cells from healthy children (aged 11–13 years) and older adults (aged 55–65 years) by using the trimodal assay TEA-seq (single-cell analysis of mRNA transcripts, surface protein epitopes and chromatin accessibility), which revealed that molecular programming of T cell subsets shifts toward a more activated basal state with age. Naive CD4 + T cells, considered relatively resistant to aging, exhibited pronounced transcriptional and epigenetic reprogramming. Moreover, we discovered a novel CD8αα + T cell subset lost with age that is epigenetically poised for rapid effector responses and has distinct inhibitory, costimulatory and tissue-homing properties. Together, these data reveal new insights into age-associated changes in the T cell compartment that may contribute to differential immune responses.
Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade
Authors: Emily C. Harrold, Michael B. Foote, Benoit Rousseau, Henry Walch, Yelena Kemel, Allison L. Richards, Fergus Keane, Andrea Cercek, Rona Yaeger, Dana Rathkopf, Neil H. Segal, Zalak Patel, Anna Maio, Matilde Borio, Eileen M. O’Reilly, Diane Reidy, Avni Desai, Yelena Y. Janjigian, Yonina R. Murciano-Goroff, Maria I. Carlo, Alicia Latham, Ying L. Liu, Michael F. Walsh, David Ilson, Jonathan E. Rosenberg, Arnold J. Markowitz, Martin R. Weiser, Anthony M. Rossi, Chad Vanderbilt, Diana Mandelker, Chaitanya Bandlamudi, Kenneth Offit, Michael F. Berger, David B. Solit, Leonard Saltz, Jinru Shia, Luis A. Diaz, Zsofia K. Stadler
Journal: Nature Medicine (2023)
Spatial transcriptomics reveals the distinct organization of mouse prefrontal cortex and neuronal subtypes regulating chronic pain
Authors: Aritra Bhattacherjee, Chao Zhang, Brianna R. Watson, Mohamed Nadhir Djekidel, Jeffrey R. Moffitt, Yi Zhang
Journal: Nature Neuroscience (2023)

Abstract The prefrontal cortex (PFC) is a complex brain region that regulates diverse functions ranging from cognition, emotion and executive action to even pain processing. To decode the cellular and circuit organization of such diverse functions, we employed spatially resolved single-cell transcriptome profiling of the adult mouse PFC. Results revealed that PFC has distinct cell-type composition and gene-expression patterns relative to neighboring cortical areas—with neuronal excitability-regulating genes differently expressed. These cellular and molecular features are further segregated within PFC subregions, alluding to the subregion-specificity of several PFC functions. PFC projects to major subcortical targets through combinations of neuronal subtypes, which emerge in a target-intrinsic fashion. Finally, based on these features, we identified distinct cell types and circuits in PFC underlying chronic pain, an escalating healthcare challenge with limited molecular understanding. Collectively, this comprehensive map will facilitate decoding of discrete molecular, cellular and circuit mechanisms underlying specific PFC functions in health and disease.
Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial
Authors: Stephen A. Harrison, Rebecca Taub, Guy W. Neff, K. Jean Lucas, Dominic Labriola, Sam E. Moussa, Naim Alkhouri, Mustafa R. Bashir
Journal: Nature Medicine (2023)

Abstract Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. MAESTRO-NAFLD-1 was a 52-week randomized, double-blind, placebo-controlled phase 3 trial evaluating the safety of resmetirom in adults with nonalcoholic fatty liver disease and presumed NASH. Patients were randomized to three double-blind arms (100 mg resmetirom ( n = 325), 80 mg resmetirom ( n = 327) or placebo ( n = 320)) or open-label 100 mg resmetirom ( n = 171). The primary end point was incidence of treatment-emergent adverse events (TEAEs) over 52 weeks and key secondary end points were LDL-C, apoB, triglycerides (over 24 weeks), hepatic fat (over 16 and 52 weeks) and liver stiffness (over 52 weeks). Resmetirom was safe and well tolerated. TEAEs occurred in 86.5% (open-label 100 mg resmetirom), 86.1% (100 mg resmetirom), 88.4% (80 mg resmetirom) and 81.8% (placebo) of patients. TEAEs in excess of placebo included diarrhea and nausea at the initiation of treatment. Key secondary end points included least square means difference from placebo at 80 mg, 100 mg resmetirom: LDL-C (−11.1%, −12.6%), apoB (−15.6%, −18.0%), triglycerides (−15.4%, −20.4%), 16-week hepatic fat (−34.9%, −38.6%), ( P &lt; 0.0001) and liver stiffness (−1.02, −1.70) and 52-week hepatic fat (−28.8, −33.9). These findings demonstrate resmetirom was safe and well tolerated in adults with presumed NASH, supporting a role for further clinical development. (ClinicalTrials.gov identifier NCT04197479 ).
Efficacy and safety of apremilast in patients with moderate-to-severe genital psoriasis: Results from DISCREET, a phase 3 randomized, double-blind, placebo-controlled trial
Authors: Joseph F. Merola, Lawrence Charles Parish, Lyn Guenther, Charles Lynde, Jean-Philippe Lacour, Petra Staubach, Sue Cheng, Maria Paris, Hernan Picard, Cynthia Deignan, Shauna Jardon, Mindy Chen, Kim A. Papp
Journal: Journal of the American Academy of Dermatology (2023)

Background Genital psoriasis can be stigmatizing, is highly prevalent among patients with psoriasis, and has limited treatment options. Apremilast is a unique oral immunomodulating phosphodiesterase 4 inhibitor approved for psoriasis treatment. Objective To assess the efficacy and safety of apremilast 30 mg twice daily in patients with genital psoriasis. Methods DISCREET, a phase 3, placebo-controlled trial (NCT03777436), randomized patients with moderate-to-severe genital psoriasis (stratified by affected body surface area <10% or ≥10%) to apremilast or placebo for a 16-week period, followed by an apremilast extension period. Week 16 results are presented. Results Patients were randomized to apremilast (n=143) or placebo (n=146). At Week 16, 39.6% and 19.5% of apremilast and placebo patients, respectively, achieved a modified static Physician Global Assessment (PGA) of Genitalia response (primary endpoint; score of 0/1, ≥2-point reduction); treatment difference was significant (20.1%, P=0.0003). Improvements in genital signs and symptoms, skin involvement, and quality of life (QoL) were observed. Common treatment-emergent adverse events were diarrhea, headache, nausea, and nasopharyngitis. Limitations Lack of active-comparator. Conclusions Apremilast demonstrated statistically and clinically meaningful genital PGA responses and improvement of signs, symptoms, severity, and QoL in this first randomized, controlled study of an oral systemic treatment in patients with genital psoriasis.
A model of conceptual bootstrapping in human cognition
Authors: Bonan Zhao, Christopher G. Lucas, Neil R. Bramley
Journal: Nature Human Behaviour (2023)

Abstract To tackle a hard problem, it is often wise to reuse and recombine existing knowledge. Such an ability to bootstrap enables us to grow rich mental concepts despite limited cognitive resources. Here we present a computational model of conceptual bootstrapping. This model uses a dynamic conceptual repertoire that can cache and later reuse elements of earlier insights in principled ways, modelling learning as a series of compositional generalizations. This model predicts systematically different learned concepts when the same evidence is processed in different orders, without any extra assumptions about previous beliefs or background knowledge. Across four behavioural experiments (total n = 570), we demonstrate strong curriculum-order and conceptual garden-pathing effects that closely resemble our model predictions and differ from those of alternative accounts. Taken together, this work offers a computational account of how past experiences shape future conceptual discoveries and showcases the importance of curriculum design in human inductive concept inferences.
The landscape of small nucleolar RNA expression in multiple myeloma is determined by cytogenetic alterations
Authors: Duoduo Zhao, Christian Rohde, Stefanie Göllner, Fengbiao Zhou, Cornelius Pauli, Maximilian Felix Blank, Rafael Zinz, Anna Luise Grab, Alexandra M. Poos, Lukas John, Stefanie Huhn, Marc-Steffen Raab, Carsten Müller-Tidow, Niels Weinhold
Journal: Leukemia (2023)
An in vitro-transcribed circular RNA targets the mitochondrial inner membrane cardiolipin to ablate EIF4G2+/PTBP1+ pan-adenocarcinoma
Authors: Zunyong Feng, Xuanbo Zhang, Jing Zhou, Qiang Li, Liuxi Chu, Guangfu Di, Zhengyuan Xu, Qun Chen, Ming Wang, Xiaochun Jiang, Hongping Xia, Xiaoyuan Chen
Journal: Nature Cancer (2023)
Data-driven identification of total RNA expression genes for estimation of RNA abundance in heterogeneous cell types highlighted in brain tissue
Authors: Louise A. Huuki-Myers, Kelsey D. Montgomery, Sang Ho Kwon, Stephanie C. Page, Stephanie C. Hicks, Kristen R. Maynard, Leonardo Collado-Torres
Journal: Genome biology (2023)

Abstract We define and identify a new class of control genes for next-generation sequencing called total RNA expression genes (TREGs), which correlate with total RNA abundance in cell types of different sizes and transcriptional activity. We provide a data-driven method to identify TREGs from single-cell RNA sequencing data, allowing the estimation of total amount of RNA when restricted to quantifying a limited number of genes. We demonstrate our method in postmortem human brain using multiplex single-molecule fluorescent in situ hybridization and compare candidate TREGs against classic housekeeping genes. We identify AKT3 as a top TREG across five brain regions.